POS0827 CLINICAL OUTCOMES OF PATIENTS WITH RHEUMATOID ARTHRITIS WHO DISCONTINUED TOFACITINIB OR TUMOUR NECROSIS FACTOR INHIBITORS: RESULTS FROM ORAL SURVEILLANCE
Authors: S. B. Cohen, H. Schulze-Koops, J. Pope, D. Gold, M. J. Cadatal, G. Schroeder, A. Diehl, E. Nagy, S. Duench, A. Rubbert-Roth
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Switching or discontinuing therapy may occur in patients (pts) with rheumatoid arthritis (RA) with an inadequate response/intolerance to treatment. In ORAL Surveillance, a post-authorisation safety study of tofacitinib vs tumour necrosis factor inhibitors (TNFi) in pts with RA despite methotrexate aged ≥50 years with ≥1 additional cardiovascular risk factor,<sup>[1]</sup> pts could discontinue the assigned study drug and switch to local standard of care (SOC) treatment and, in contrast to previous randomised controlled trials, were encouraged to remain in the study. <h3>Objectives</h3> To assess efficacy/safety in the SOC period in pts who discontinued study drug and started SOC treatment. <h3>Methods</h3> This post hoc analysis included randomised pts from ORAL Surveillance (NCT02092467) who received ≥1 dose of study drug (tofacitinib 5 or 10 mg twice daily [BID], or TNFi) and initiated SOC treatment per-protocol after discontinuing study drug. SOC treatment could include disease-modifying antirheumatic drugs (DMARDs; biologic, targeted synthetic, or conventional synthetic [cs]), or glucocorticoids. Efficacy outcomes included mean observed and change from randomisation/SOC baseline (BL; Δ) in Simplified Disease Activity Index (SDAI) over time. Adverse events (AEs) and serious AEs (SAEs) were reported; incidence rates (IRs; pts with events/100 pt-years [PY]) were estimated for AEs of special interest (AESI). Data were analysed for the periods in which pts who discontinued study drug received 1) tofacitinib or TNFi (randomised period) and 2) SOC treatment (SOC period). Pts were analysed in their original treatment group (ex-tofacitinib 5/10 mg BID, or ex-TNFi). Analyses were descriptive. <h3>Results</h3> Of 4362 randomised and treated pts, 718 (16.5%) stopped study drug (50.7, 59.3 and 47.8% due to AEs; 15.1, 5.8 and 21.9% due to insufficient clinical response for tofacitinib 5 mg BID, 10 mg BID and TNFi, respectively); most received csDMARDs only in the SOC period (73.1–79.6% across groups). In general, BL characteristics in pts who switched to SOC treatment were numerically similar across groups. Mean duration of randomised and SOC periods was 21.9–26.0 and 15.0–18.6 months, respectively. ΔSDAI over time was similar across groups in the randomised period (data not shown) with modest improvements in the SOC period (Figure 1) and with SDAI score generally reflecting moderate disease activity (data not shown). In general, AE and SAE rates were similar across groups but numerically higher in the randomised vs SOC period (data not shown). AESI rates were generally similar across groups in the SOC period (Table 1). <h3>Conclusion</h3> In ORAL Surveillance, pts with RA who discontinued tofacitinib or TNFi and switched to SOC treatment had modest improvements in efficacy over time without increased risk of AEs. Limitations included that this analysis was post hoc. <h3>Reference</h3> [1]Ytterberg et al. N Engl J Med 2022; 386: 316-26 <h3>Acknowledgements</h3> This study was sponsored by Pfizer. Medical writing support, under the direction of the authors, was provided by Maisie Camm, BSc, CMC Connect, a division of IPG Health Medical Communications, and was funded by Pfizer, New York, NY, USA, in accordance with Good Publication Practice (GPP 2022) guidelines (Ann Intern Med 2022;175:1298-1304). <h3>Disclosure of Interests</h3> Stanley B. Cohen Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Gilead Sciences, Merck and Pfizer Inc, Hendrik Schulze-Koops Consultant of: AbbVie, Amgen, Biogen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead Sciences, Hexal Sandoz, Hospira, Janssen-Cilag, MSD, Novartis, Pfizer Inc, Roche and UCB, Grant/research support from: Novartis and Pfizer Inc, Janet Pope Consultant of: AbbVie, Actelion, Amgen, Bayer, Bristol Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer Inc, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Bristol Myers Squibb, Roche, Seattle Genetics and UCB, David Gold Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Mary Jane Cadatal Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Georgene Schroeder Employee of: Syneos Health, who were paid contractors to Pfizer Inc, Annette Diehl Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Edward Nagy Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Stephanie Duench Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Andrea Rubbert-Roth Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Janssen and Sanofi Pasteur, Consultant of: AbbVie, Amgen, Chugai, Eli Lilly, F. Hoffmann-La Roche, Gilead Sciences, Novartis and Sanofi Pasteur.